Vascular prosthesis for leak prevention during endovascular aneurysm repair

ABSTRACT

An embodiment includes a process for treating an abdominal aortic aneurysm (AAA) endoleak with a shape memory polymer (SMP) foam device. First, a bifurcated stent graft is placed within the aneurysm while a micro guidewire is positioned within the aneurysm for future catheter access. Second, after placing the iliac graft extension, a catheter is introduced over wire to deliver embolic foams. Third, embolic foams expand and conform to the aneurysm wall. Fourth, embolic foams create a stable thrombus to prevent endoleak formation by isolating peripheral vessels from the aneurysm volume.

CROSS-REFERENCE TO RELATED APPLICATION

This application claims priority to U.S. Provisional Patent ApplicationNo. 62/609,268 filed on Dec. 21, 2017 and entitled “Shape Memory PolymerFoams for Endoleak Prevention During Endovascular Aneurysm Repair”, thecontent of which is hereby incorporated by reference.

TECHNICAL FIELD

Embodiments of the invention are in the field of prosthesis (e.g.,artificial body members) such as, for example, an arterial prosthesis.

BACKGROUND

Endovascular aneurysm repair (EVAR) is a technology for treatingabdominal aortic aneurysms (AAA), wherein a stent graft is deployed toexclude the aneurysm from systemic circulation. However, commoncomplications associated with EVAR treatments include endoleaks (bloodflow outside the stent graft) and graft migration, both of which requirefrequent follow-up due to the risk of aneurysm growth and potentialrupture. Should endoleaks occur, they may require reintervention withembolic materials to occlude the source of the endoleak.

BRIEF DESCRIPTION OF THE DRAWINGS

Features and advantages of embodiments of the present invention willbecome apparent from the appended claims, the following detaileddescription of one or more example embodiments, and the correspondingfigures. Where considered appropriate, reference labels have beenrepeated among the figures to indicate corresponding or analogouselements.

FIG. 1 depicts four stages of a process in an embodiment.

FIG. 2 depicts characteristics of various embodiments.

FIG. 3 shows various amplifications of foam embodiments.

FIG. 4 shows various aneurysm shapes suitable for treatment withembodiments.

FIGS. 5A-5G show various deployment stages and configurations in variousembodiments.

DETAILED DESCRIPTION

Reference will now be made to the drawings wherein like structures maybe provided with like suffix reference designations. In order to showthe structures of various embodiments more clearly, the drawingsincluded herein are diagrammatic representations of structures. Thus,the actual appearance of the fabricated structures, for example in aphoto, may appear different while still incorporating the claimedstructures of the illustrated embodiments. Moreover, the drawings mayonly show the structures useful to understand the illustratedembodiments. Additional structures known in the art may not have beenincluded to maintain the clarity of the drawings. “An embodiment”,“various embodiments” and the like indicate embodiment(s) so describedmay include particular features, structures, or characteristics, but notevery embodiment necessarily includes the particular features,structures, or characteristics. Some embodiments may have some, all, ornone of the features described for other embodiments. “First”, “second”,“third” and the like describe a common object and indicate differentinstances of like objects are being referred to. Such adjectives do notimply objects so described must be in a given sequence, eithertemporally, spatially, in ranking, or in any other manner “Connected”may indicate elements are in direct physical or electrical contact witheach other and “coupled” may indicate elements co-operate or interactwith each other, but they may or may not be in direct physical orelectrical contact. Phrases such as “comprising at least one of A and B”include situations with A, B, or A and B.

In the past embolic materials have been investigated as suitable optionsfor aneurysm embolization and endoleak prevention. However, Applicantdetermined the elastic expansion force of such materials against thecatheter wall generates significant device friction during delivery. Theincrease in device friction leads to stiffer delivery wires, lesstactile feedback during deployment, and a decrease in volumetricfilling. Applicant also determined that additional materials that havebeen investigated for prevention of endoleaks have limitations withregard to device surface area, volume, and thrombogenicity, which leadsto numerous devices being required to fill the aneurysmal space andprolonged treatment times.

In contrast, embodiments described herein include a polyurethane shapememory polymer (SMP) foam that functions as an effective embolizationdevice with favorable healing responses and relatively low frictionduring delivery due to the shape memory effect. These foam devices arecapable of volume expansions of up to 70× or more to provide efficientvolumetric filling without generating significant pressure on theaneurysm wall and can be delivered through tortuous pathways with lowfriction via catheterization. Such foam embodiments function as anembolic agent and subsequent scaffold for a healthy healing response,which makes them ideal for a catheter delivered whole foam devices forendoleak prevention during EVAR.

Applicant further determined the advantage of providing visibility forthe entire foam length. For this reason, embodiments include radiopaqueSMP foam formulations designed for X-ray visibility, as well asalternative means of visualizing the entire foam length. Thesealternative means of visualization include the use of a radiopaque fiberor coil that extends through the core and spans the entire devicelength. The termination point of the radiopaque fiber or coilcorresponds to the distal and/or proximal tip of the SMP foam toindicate where one or both ends of the device are located.Alternatively, a radiopaque marker band may be used on one or both ofthe proximal and distal ends of the device to indicate where both endsof the device are located under X-ray.

Applicant further determined previously known SMP foam chemistries areinherently oxidatively degraded during the healing process in vivo bymacrophages and neutrophils. However, certain embolization indicationsbenefit from a permanent, compliant scaffold, like an SMP foam, sincethe risk of recanalization may increase if the embolic material degradesprior to complete healing in the body. Additionally, certainindications, such as AAA's and endoleaks may require very large volumesof SMP foams to be implanted to effectively treat the patient. In theselarge volumes, degradation byproducts may cause unknown complicationsdue to the large concentration of compounds in one region subjected toslow clearance rates. Due to these risks of recanalization and potentialtoxic byproducts, embodiments include a biodurable, or non-degradable,SMP foam formulation for use in these indications which require largevolumes of permanent embolic materials.

Broader Impacts

Applicants determined there is a medical need for a technology that willreduce the number of endoleaks, secondary interventions, and monitoringof patients who have undergone EVAR for AAA's. SMP foam embodiments forperigraft embolization of AAA's provide a safe and effective means tomitigate the occurrence of EVAR complications. The embolization deviceembodiments described herein save patients thousands of dollars inpost-EVAR management, prevent life-threatening complications, and havean impact on the healthcare industry through reimbursement based onsuperior clinical outcomes.

General

Embodiments take a materials science approach to address the unmetclinical need of endoleak treatment and prevention. This is accomplishedthrough thermomechanical optimization of SMPs. The embodiments address,for example:

Optimized SMP foam morphology, expansion behavior, expanded devicegeometry, and delivery platform that enables consistent device deliverythrough 5-9F catheters and sheaths.

Verified device delivery, device expansion, and perigraft flow stasiswithin an EVAR treated AAA benchtop flow model with simulated endoleak.

Device Safety and Efficacy.

Thus, embodiments prove the feasibility of the AAA embolic foam devicein vitro and in vivo. Embodiments are viable adjuncts to endovascularaneurysm repair procedures as a prophylactic against endoleak formation.

Significance

Until the past decade, the traditional method of AAA repair was opensurgery, but since 2006, EVAR has been preferred to open surgicalrepair, accounting for 74% of all AAA treatments. Although open surgeryrepair and EVAR have similar long term survival rates of 69.9% and68.9%, respectively, the procedural preference for EVAR is motivated byshorter hospital stays, less blood loss, shorter operating times, andlower early morbidity and mortality. Despite the advantages of EVAR, ashigh as 32% of the 33,000 annual EVAR procedures in the US can stillresult in some type of endoleak. Endoleak, as used herein, is defined asblood flow outside of the stent graft but within the aneurysm sac, whichcan result in aneurysm enlargement and rupture. The origin of the leakdefines the type of endoleak, but all or most types are typicallymonitored with long term surveillance or addressed with subsequentsurgical procedures. New endoleaks have developed as long as severalyears post procedure, which necessitates long term patient screening.

As more patients are opting for EVAR, there is a strain on healthcaresystems to cover the cost. Long-term surveillance, imaging studies, andreintervention have been shown to increase the global cost of EVAR bynearly 50%. According to recent meta-analyses, EVAR has a 56% greaterintermediate reintervention rate and 243% greater long-termreintervention rate when compared to open surgical repair. Despite morecompliant stent-graft technology and more surgical experience, EVARremains less durable than open repair. Long-term durability of EVARsuffers due to endoleak development, graft migration, and continued sacpressurization, all of which may result in sac rupture. Despite newtechnology for stent-grafts, the amount of people who develop endoleakshas not significantly decreased, partly as a result of endografts beingimplanted outside of their instructions for use (IFU) and the inabilityto effectively prevent type II endoleaks.

Embodiments help prevent or mitigate endoleaks and may liberalize theIFU for stent-grafts, reduce EVAR complications related to endoleak, andreduce the amount of stringent post-EVAR imaging. The benefits of suchembodiments will have a positive impact economically, physically, andmentally on patients due to increased EVAR durability and reducedmonitoring. Accordingly, embodiments that reduce the development andseverity of endoleaks will improve cost effectiveness and durability ofEVAR.

Type I (T1) and type III (T3) endoleaks have been treated by coilembolization, angioplasty, additional endografts, or glue embolization.However, management for type II (T2) endoleaks remains controversialdespite being the most common type of endoleak. Unlike T1 and T3endoleaks, T2 endoleaks can spontaneously resolve and their relationshipto aneurysm sac enlargement and pressurization are uncertain. There is aconsensus, however, that persistent T2 endoleaks (>6 months) areassociated with aneurysm sac growth, reintervention, conversion to openrepair, and rupture. Furthermore, the detection and embolization of T2endoleaks is difficult due to the size of feeding vessels. As a resultof inadequate detection of endoleaks and the ability of endoleaks toresolve then reappear, patients are monitored yearly. Regardless of thetype of endoleak, embodiments address a clinical need to make EVAR moredurable and to exclude the aneurysm from systemic circulation. Sacembolization at the time of EVAR has been studied in an effort to reduceendoleak development. These prophylactic embodiments reduce the need forlong-term surveillance, prevent endograft migration via biologicalfixation, and mitigate endoleak formation. Embodiments utilize SMPmaterials that have advantages over more conventional materials. Thoseadvantages relate to, for example, cytotoxicity, potential to createcolonic ischemia, insufficient control and predictability, difficultdelivery, incomplete occlusion, and recanalization.

Expandable polyurethane foam embodiments are used in embodiments due totheir excellent acute thrombogenicity, long term biocompatibility,tunable pore size, and favorable healing response. Polyurethane SMP foamembodiments are used in catheter-based embolic devices because they candeform into a secondary shape for delivery purposes, and subsequentlyactuate to their primary shape using stimuli such as heat. Embodimentsleverage the ability of polyurethane SMPs to thermally expand at bodytemperature after being delivered via catheterization to treat andprevent endoleaks, as well as to mitigate complications of EVAR.Embodiments enable development of therapeutic and preventativetreatments of AAA to lessen the burden of long-term monitoring,secondary intervention, and lifetime cost of EVAR.

Embodiments include ultra-low density SMP polyurethane foams withcustomizable glass transition temperatures, 98% shape recovery, a glassystorage modulus of 200-300 kPa, and recovery stresses of 5-15 kPa. Thesematerials are synthesized from low-molecular weight branched monomers,and undergo foaming to create highly chemically crosslinked, highlyporous, low density network structures. This high crosslink densityprevents “secondary-shape forming” from occurring in the SMPpolyurethane foams, which preserves the primary shape and improves theshelf life of the device by reducing the likelihood of chain relaxation.The foams also have porosities as high as 98.8%, which allow the foamsto serve as a scaffold for tissue ingrowth and enables greatervolumetric expansions when compared to neat SMPs. Further, theinterconnected porous geometry of the material improves embolization bypromoting flow stasis and providing a large surface area to trigger theintrinsic clotting cascade.

FIG. 1 outlines an embodiment of a process for treating AAA endoleakwith whole SMP foam devices. At stage 1 a bifurcated stent graft (a) isplaced within the aneurysm while a micro guidewire (b) is positionedwithin the aneurysm for future catheter access. At stage 2, afterplacing the iliac graft extension (c), a 5F catheter (d) is introducedover wire (b) to deliver embolic foams (e). At stage 3 embolic foamsexpand and conform to the aneurysm wall (f). At stage 4 embolic foamscreate a stable thrombus to prevent endoleak formation by isolatingperipheral vessels (g) from the aneurysm volume.

Despite SMP foam low density and lack of inherent X-ray attenuation,embodiments of SMP polyurethanes are made radiopaque through theincorporation of tungsten particles into the polymer structure. Byloading 4% by volume of tungsten into SMP foams, radio-opacity isachieved while maintaining favorable mechanical, morphological, andchemical properties of unloaded foams. Solid polymer, polymer foams, andcrimped foams of different geometries were mounted to a porcine head tomimic the density of a human skull and were imaged under fluoroscopy.Doped SMP with 4% by volume tungsten were visible under fluoroscopy.More specifically, 4% tungsten-doped SMP cylinders of various mmthicknesses imaged via fluoroscopy with a pig's skull providing relativeradio opacity. The cylinders were visible.

Additionally, tungsten doped SMP foams were implanted into a vein pouchporcine aneurysm model and resulted in dense cellular connective tissueinfiltrating the foam with minimal inflammation. When viewed underscanning electron microscopy (SEM), tungsten particles were encapsulatedin polymer matrix that remained intact after 90 days in vivo, suggestingnon-toxic leaching. Tensile testing of non-loaded foams compared withtungsten loaded foams showed an increase in toughness and 43% increasein modulus. SEM images showed greater cell density as a result oftungsten particles, which contributes to the increased stiffness of thefoams. Finally, glass transition temperatures did not changesignificantly with the addition of tungsten. The results from theseinvestigations emphasize the clinical feasibility of embodiments to bedelivered safely into an AAA sac under fluoroscopy while maintainingfavorable volumetric expansion and biocompatibility.

Embodiments demonstrate that SMP polyurethane foams are a class ofmaterials that have unique properties adept at aneurysm filling. Thesematerials provide an effective and safe preventative treatment againstthe development of endoleaks, and may reduce the long-term surveillancethat is necessary for EVAR. Prophylactic treatment of AAAs could improvethe long-term durability of EVAR and reduce the high number of secondaryinterventions many EVAR patients undergo, usually as a consequence ofendoleak or graft migration. Additionally, embodiments may liberalizethe instructions for use for many stent-graft procedures, allowingotherwise untreatable AAAs the ability to be repaired. The developmentand further characterization of SMP polyurethane foams can also beapplied to many other embolic or vascular occlusion devices.

Issue 1: Embodiments optimize the SMP foam morphology, expansionbehavior, expanded device geometry, and delivery platform to enableconsistent device delivery through a 5F catheter.

Embodiments provide an actuation method that has a delayed expansionusing body temperature and the aqueous environment of the blood. Theactuation kinetics of the foam are tailored by altering the glasstransition temperature (T_(g)) relative to body temperature and alteringthe bulk foam hydrophobicity to control the moisture plasticizationrate. Both T_(g) and hydrophobicity are altered by varying thediisocyanate monomer ratios within the polyurethane synthesis. As shownin FIG. 2 (where at 10 min reticulated foam is highest and the controlis lowest in diameter), the actuation profile of the foam can be furtheroptimized by using cold plasma surface functionalization with twodifferent approaches (Aurora 350, Plasma Technology Systems). First,hydrocarbon process gasses (e.g. acetylene, ethylene, propylene) depositan aliphatic water diffusion barrier to slow the moisture plasticizationrate and delay passive foam expansion. Second, oxygen andtetraflouromethane process gasses create an oxidative atmosphere to etchthe polymer membranes, creating a highly reticulated foam structure withhigher surface hydrophilicity, which both contribute to faster foamexpansion.

More specifically, FIG. 2 shows foams with varying surface modificationsdisplay different expansion kinetics when submersed in 37° C. water.Foams were fabricated with an isocyanate ratio of 70% hexamethylenediisocyanate, 30% trimethylhexamethylene diisocyanate. The plasmareticulation atmosphere consisted of oxygen and tetraflouromethaneionized at 300 W for 30 seconds. The hydrocarbon plasma atmosphereconsisted of acetylene and propylene ionized at 150 W for 2 minutes.

By tailoring the bulk hydrophobicity of the foam and the diffusioncharacteristics of the surface, the actuation profile of the foam istailored for delayed expansion. Controlled delay prevents the devicefrom deploying and binding within the delivery catheter, but stillallows the foam to expand and fill the aneurysm anatomy at bodytemperature without an external heating source.

FIG. 3 shows the expanded and crimped morphologies of SMP devices invarious embodiments. The left panel of FIG. 3 shows a comparison betweenan expanded 10 mm diameter tungsten doped SMP foam device and a crimped1.3 mm diameter SMP device loaded into a 5F catheter. SEM images showthe expanded morphology of a reticulated foam along the foaming axis(axial, middle panel) and orthogonally (transverse, right panel).

A delivery platform incorporating an introducer device and delivery wirefacilitate quick and safe delivery of crimped SMP devices through thecatheter and into the aneurysm site. Introducer devices enable the saferemoval of air from the foams through a series of flushes and hemostaticvalves.

Issue 2: Embodiments verify device delivery, device expansion, andperigraft flow stasis within an EVAR treated AAA benchtop flow modelwith simulated endoleak.

Silicone vascular phantoms representing idealized and physiologic AAAanatomies were fabricated and incorporated into flow loops atphysiologic temperature. Expired EVAR grafts were placed within thephantoms with secondary flow channels providing simulated T2 endoleakflow. Graft placement was modified to simulate a T1 or T3 endoleak. FIG.4 depicts several phantom designs. More specifically, FIG. 4 shows fromleft to right: Large idealized AAA model with renal arteries, idealizedAAA model with collateral vessels to mimic type II endoleak, and a CTreconstructed AAA model.

SMP foam devices were delivered into the pseudo-aneurysm sac via a 5Fcatheter to emulate clinical delivery. Flow stasis may be quantified bythe time it takes the dye to clear the aneurysm space when compared to abaseline value prior to foam implantation. This metric helps quantifythe probability of sufficient flow stasis for embolization within theaneurysm and subsequent endoleak stabilization.

Issue 3: Embodiments demonstrate device safety and efficacy in a pilotanimal study using a porcine AAA animal model.

Domestic swine weighing approximately 20 kilograms underwent surgery tocreate an aneurysm in the abdominal aorta. A vascular stent graft wasdeployed to isolate the surgically created abdominal aortic aneurysm,followed by the delivery of embolic foams through a 6-8F catheter toocclude the perigraft space. Three-dimensional computerized tomographyangiography (3D-CTA), conventional angiography, and X-ray was performedprior to and following foam treatment to observe the presence ofendoleak and determine the extent of acute embolization.

Additional Embodiments

An embodiment provides a solution to prevent endoleaks by filling thevoids within sequestered regions by conforming to the contours of thescaffold/graft and the physiologic environment, creating rapid thrombusformation and obstruction of systemic blood flow, eventually leading toscar tissue formation and permanent exclusion of blood flow through thesequestered region.

The foam material utilized in an embodiment allows compression fordelivery through small caliber delivery catheters with subsequentexpansion in diameter or length to fill large volumes. Upon expansion,the foams induce thrombosis via flow stagnation, activation of theintrinsic clotting cascade upon blood contact with the foam material,and activation of the extrinsic clotting cascade upon foam contact withthe inner surface of the vessel or aneurysm. This prevents continuedblood flow through or into the sequestered region, and leads to eventualconnective tissue infiltration into the foam volume or the volumepreviously occupied by foams and permanent healing at the site of thevascular anomaly. This strengthens the once susceptible region that wassequestered and reduces the risk of vessel injury or rupture.

The ability of foam embodiments to cause flow stagnation within thevasculature and the ability to promote significant connective tissueinfiltration over time after initial thrombosis differ from priormethods. Such prior methods intended to fill the void space within asequestered region with a material to exclude the void space and providesemi-rigid support of the surrounding environment. In contrast, thefoams of embodiments conform to fill the void space within thesequestered region, remain compliant throughout the treatment lifetime,and allow the sequestered region to heal over time rather than applyingconstant pressure to the susceptible region. Embodiments use foams thatare biodegradable or biodurable implants, and both types of foam providea scaffold for future connective tissue infiltration while alsoremaining compliant to the surrounding environment.

An embodiment of SMP foam includes a 100% hexamethylenediisocyanate(HDI) foam for the isocyanate component of the polyurethane (PU) foam.However, other embodiments include 95, 90, 85, 80, 75, 70, 65, 60% orless HDI. The remainder of such foams may include isocyanate componentstaken from, for example, trimethylhexanediisocyanate (TMHDI) and/orisophorone diisocyanate (IPDI), and the like. The high HDI contentpromotes faster expansion of the foam. Embodiments may also include keyratios for polyfunctional alcohol content of the PU foam. For example,an embodiment foam may be formed from triethanolamine (TEA) and tetrakis(2-hydroxyl propyl) ethylenediamine (HPED). The ratio between these twoalcohols is 80:20 to further promote rapid expansion/actuation of thefoams. However, other embodiments may include ratios of 90:10, 70:30,60:40, and 50:50 between the two alcohols and other embodiments mayinclude other alcohols entirely.

Embodiments may include a radiopaque foam, and/or biodurable foams. Thefollowing provide examples of radiopaque and/or biodurable foams.

Example 1a includes a system comprising: a thermoset shape memorypolymer (SMP) foam that is covalently bonded to iodine; wherein (a) theSMP foam is configured to expand from a compressed secondary state to anexpanded primary state in response to thermal stimulus, and (b) the SMPfoam is a poly(urethane-urea-amide).

Example 2a includes the system of example 1a wherein the SMP foam isradiopaque.

Example 3a includes the system of example 2a wherein the iodine isincluded in a triiodobenzene monomer.

Example 4a includes the system of example 3a wherein the triiodobenzenemonomer includes at least one of (a) 5-amino-2,4,6-triiodoisophthalicacid (ATIPA), (b) diatrizoic acid, (c) iohexol, and (d) triiodophenol.

Example 5a includes the system of example 4a wherein the triiodobenzenemonomer includes ATIPA.

Example 6a includes the system of example 5a wherein the ATIPAcrosslinks polymer chains of the SMP foam.

Another version of example 6a includes the system of example 5a wherein(a) the ATIPA crosslinks polymer chains of the SMP foam, and (b) anothercrosslinking agent crosslinks polymer chains of the SMP foam.

Example 7a includes the system of example 3a wherein the SMP foamincludes at least one of platinum, tungsten, and tantalum, the at leastone of platinum, tungsten, and tantalum being physically bound withinthe SMP foam.

Example 8a includes the system of example 7a wherein the at least one ofplatinum, tungsten, and tantalum is not chemically bound to the SMPfoam.

Example 9a includes the system of example 3a comprising a backbone thattraverses the SMP foam, wherein the backbone includes at least one of apolymer filament and a metal.

Example 10a includes the system of example 9a wherein the backboneincludes a polymer filament and no metal.

In other version of Example 10a the backbone includes a polymer but nometal. In other version of Example 10a the backbone includes a majority% of polymer and a minority % of metal.

Example 11a includes a method comprising: providing a triiodobenzenemonomer; providing an aliphatic monomer comprising at least one of(a)(i) multiple amine functional groups, (a)(ii) multiple alcoholfunctional groups, and (a)(iii) multiple carboxylic acid functionalgroups; providing a diisocyanate; mixing the triiodobenzene monomer, thealiphatic monomer, and the diisocyanate into a solution; forming athermoset shape memory polymer (SMP) foam from the solution.

Example 12a includes the method of example 11a wherein: triiodobenzenemonomer includes a first member selected from the group consisting of5-amino-2,4,6-triiodoisophthalic acid (ATIPA), diatrizoic acid, iohexol,or triiodophenol; the aliphatic monomer includes a second memberselected from the group consisting of 1,2,6-hexanetriol (HT);2-butyl-2-ethyl-propanediol (BEP); 3-methyl-1,5-pentanediol (MPD);diethylene glycol (DEG); triethylene glycol (TEG); triethanolamine(TEA); tetrakis-hydroxypropyl ethylenediamine (HPED); glycerol;trimethylolpropane; trimethylolmethane; 1,2,4-butanetriol;1,2-diaminopropane; 2,2-Dimethyl-1,3-propanediamine; 1,8-Diaminooctane;3-Amino-1,2-propanediol; 2-Amino-2-methyl-1,3-propanediol;1,3-Diamino-2-propanol; or aspartic acid; the diisocyanate includes athird member selected form the group consisting of hexamethylenediisocyanate (HDI); trimethylhexamethylene diisocyanate (TMHDI);isophorone diisocyanate; 1,3,4-triisocyanato-2,4,6-trimethylbenzene;toluene diisocyanate; or methylene diphenyl diisocyanate.

Example 13a includes the method of example 12a wherein the second memberis selected from the group consisting of HT; BEP; MPD; DEG; TEG; TEA;HPED; glycerol; trimethylolpropane; trimethylolmethane; or1,2,4-butanetriol.

Example 14a includes the method of example 12a wherein the second memberis selected from the group consisting of 1,2-diaminopropane;2,2-Dimethyl-1,3-propanediamine; 1,8-Diaminooctane;3-Amino-1,2-propanediol; or 2-Amino-2-methyl-1,3-propanediol.

Example 15a includes the method of example 12a wherein the third memberis selected form the group consisting of HDI; TMHDI; and isophoronediisocyanate.

Example 16a includes the method of example 12a wherein the third memberis selected form the group consisting of elected form the groupconsisting of 1,3,4-triisocyanato-2,4,6-trimethylbenzene; toluenediisocyanate; or methylene diphenyl diisocyanate.

Example 17a includes the method of example 12a wherein the first memberis ATIPA.

Another version of Example 17a includes the method of example 12awherein the first member is ATIPA and the ATIPA constitutes between 20and 30% MW of the first and second members.

Example 18a includes the method of example 12a comprising crosslinkingthe second and third members with the first member.

Example 19a includes the method of example 18a wherein forming the SMPfoam from the solution comprises utilizing the first member as achemical blowing agent.

Example 20a includes the method of example 12a wherein the aliphaticmonomer includes a fourth selected from the group consisting of HT; BEP;MPD; DEG; TEG; TEA; HPED; glycerol; trimethylolpropane;trimethylolmethane; 1,2,4-butanetriol; 1,2-diaminopropane;2,2-Dimethyl-1,3-propanediamine; 1,8-Diaminooctane;3-Amino-1,2-propanediol; 2-Amino-2-methyl-1,3-propanediol;1,3-Diamino-2-propanol; or aspartic acid;

Example 21a includes a system comprising: an iodine containing thermosetopen-cell shape memory polymer (SMP) foam that is x-ray visible; wherein(a) the SMP foam is configured to expand from a compressed secondarystate to an expanded primary state in response to thermal stimulus, (b)the SMP foam is a poly(urethane-urea-amide).

Whether something is “x-ray visible” or “radiopaque” is judged accordingto a person of ordinary skill in the art, such as a neurosurgeon orinterventional neuroradiologist that routinely treats aneurysms usingimaging, such as fluoroscopy or angiography. While x-ray power may varydepending on the imaging machine used and the like, a person of ordinaryskill in the art will still understand whether a foam is visible undernormal clinical conditions such that the foam is discernable from thesurrounding anatomy.

Example 22a includes the system of example 21a wherein the iodine isincluded in a triiodobenzene monomer and the iodine is covalently bondedwithin a polymer network of the SMP foam.

Another version of Example 22a includes the system of example 21awherein the iodine is included in a triiodobenzene monomer and theiodine is physically incorporated within the SMP foam.

Another version of Example 22a includes the system of example 21awherein the iodine is included in at least one triiodobenzene monomerand the iodine is both: (a) covalently bonded within a polymer networkof the SMP foam, and (b) physically incorporated, but not chemicallybonded, within the SMP foam.

Example 23a includes the system of example 22a wherein the SMP foam inthe secondary state contains between 50 and 500 mg/ml of Iodine.

However, other embodiments the SMT foam in the secondary state mayinclude between 50 and 100, 100 and 200, 200 and 300, 300 and 400 ormore mg/ml of Iodine.

Example 24a includes the system of example 23a wherein: the SMP foam inits primary state has a density of less than 0.1 g/cc; the SMP foam hasa dry glass transition temperature (Tg) between 30 and 100 degrees C.

Another version of Example 24a includes the system of example 23awherein: the SMP foam in its primary state has a density of less than0.1 g/cc; the SMP foam has a dry glass transition temperature (Tg)between 30 and 100 degrees C.; and the SMP foam lacks a Fouriertransform infrared spectroscopy (FTIR) urea peak at 1650 cm-1.

Other versions of Example 24a have a density of less than 0.09, 0.08,0.07, 0.06, or 0.05 g/cc.

Example 25a includes the system of example 22a wherein the SMP foamcomprises polycaprolactone (PCL).

Another version of Example 25a includes the system of example 22awherein the SMP foam comprises a hydrolytically degradable esterlinkage.

Another version of Example 25a includes the system of example 22awherein the SMP foam comprises at least one of polycaprolactone (PCL) ora different hydrolytically degradable ester linkage.

In an embodiment the graft is deployed to the region, followed by theimplantation of the foams, however, the foams may also be deployed firstand then kept in place by the placement of a graft. Other methodsinclude the method of FIG. 1.

For instance, different embodiments may vary the order in which thefoams could be deployed—(i.e., before or after the stent graft (or asimilar scaffold) is deployed across an aneurysm or cavity). One ordermay be to deploy the scaffold first, and then the foams so that thescaffold keeps the foams in place. However, in a low-flow region (forexample) an embodiment may have the foams deployed first and then thescaffold.

Alternative uses for embodiments may be to impart a specific shape on agraft or biologic structure by applying external or internal pressure tothe walls of the graft or structure.

For instance, an embodiment may include a specific shape of foam or neatpolymer. The shape may be, for example, a shape of replacement bone suchas a chin or cheek bone. The SMP could be set it into an easy-to-delivershape (e.g., columnar). A physician could then make a small incision inthe skin into which the polymer is placed into a cavity in the tissue.The SMP then subsequently expands into a perfectly shaped chin or cheekbone. Thus, embodiments may be used for orthopedic or plastic surgeryspaces (and many others) where one needs a scaffold to support skin in acertain way, but it also must remain compliant, which can beaccomplished with SMP embodiments described herein (i.e., conform to thesurroundings and remain compliant). Additionally, SMPs with higherradial forces would allow one to implant such a SMP to deflect a graftor pieces of tissue in a desired way as the foam expands from a crimpedstate to an expanded state.

An embodiment includes singular or multiple crimped foams with orwithout a core element running centrally through them loaded into anintroducer that allows them to be transferred directly into a guidecatheter using a guidewire or a pusher wire/rod.

FIGS. 5A-G show frames from videos. Such frames show SMP foam whenutilized with a graft or scaffold.

Specifically, FIGS. 5A-B address a benchtop aneurysm model. FIG. 5Ashows at least three foams deployed from a catheter. The foams are notcoupled to each other. Each foam has a radiopaque cap on one end of thefoam. A pusher rod or, more generally, a pushing element is shownemanating from a delivery conduit. The pushing element is used to pushthe foams out of the delivery conduit. FIG. 5B shows the foamsactuating/having actuated.

FIGS. 5C-G address a porcine aneurysm model. FIG. 5C shows two foamshaving been pushed out of a delivery conduit. The conduit is visible. Anon-deployed foam is shown still within the conduit. Each foam has aradiopaque cap. The foams are not coupled to each other. FIG. 5D showsat least four foams deployed along with a pushing element residentwithin the delivery conduit. FIG. 5E shows more than ten foams deployed.For example, in an embodiment a single delivery conduit may comepreloaded with five foams. To deploy ten foams a user may utilize twodeliver conduit foam systems. FIG. 5F shows many deployed foams as wellas the AAA stent graft. FIG. 5G shows how a AAA stent graft is notimpinged upon by the relatively gentle expansion of foam. Notably thediameter of the graft remains largely unchanged between before and afterfoam deployment images.

Images 5A-F show an ability for embodiments to be delivered usingminimally invasive techniques, the low density nature of the material tonot add weight to the vulnerable region, and the ability of thematerials to conform to the surrounding environment to minimize damageto surrounding tissues and structures.

This is in contrast to some conventional systems. Such systems show thatthe material used to fill the void space provided substantial added massto the stent graft system, which resulted in graft migration due togravitational effects of the material mass. There have also been issueswith embolic material migration out of the “endobag” which contains thematerial due to fracture in the endobag. There have been deaths reportedand adverse events as a result of the observations. The use of suchconventional technologies (e.g., embolic coils or glues) also achieve alesser result as substantially large numbers of coils are required tofill the space, resulting in greatly increased procedural costs and thesame risk of added mass to a vulnerable region in vivo.

Embodiments include foam devices where each of the devices includes aproximal marker band (e.g., a radio opaque band that adheres to aproximal end of the foam using an adhesive.) Such foams may not includea filament or wire that traverse the length of the foam. This mayinclude 2 to 10 foam plugs loaded into an introducer (delivery conduit).Embodiments include 2, 3, 4, 5, 6, 7, 8 or more plugs in a deliveryconduit. The plugs or foam portions may not be permanently coupled toeach other (e.g., they are merely adjacent one another in the deliveryconduit but nothing tethers or binds them together once they deploy fromthe conduit). However, in other embodiments the foams may be crimpedover a wire (which may or may not be coiled), such as a wire made fromplatinum and/or iridium. In other embodiments the foams are crimped overa length of suture, such as polypropylene suture. Other embodiments mayinclude foams crimped over a shape memory material, such as a length ofnitinol (e.g., 0.0065″ in diameter).

In an embodiment the polymer backbone of the SMP foam is modified withlinkages that degrade over time in the presence of water or oxidativespecies to create small molecules that can be cleared by the body. Thiscreates a biodegradable implant that leaves only native scar tissue inthe patient's body, which is not possible with any current endoleaktreatments.

An embodiment includes a SMP foam synthesized using polyfunctionalalcohols (triethanolamine andN,N,N′,N′-Tetrakis(2-hydroxypropyl)ethylenediamine), diisocyanatemonomers (triemethylhexamethylene diisocyanate, hexamethylenediisocyanate, isophorone diisocyanate), blowing agents, surfactants, andcatalysts. Polyfunctional alcohols containing water labile linkages suchas anhydride or ester linkages could also be included in the foam tofacilitate hydrolytic biodegradation. Alternatively, monomers caninclude tertiary amines or ether linkages to facilitate oxidativebiodegradation. The foam is doped with radio-opaque particles during thefoaming process to facilitate visualization under fluoroscopy duringendovascular placement. The foam components are homogeneously mixed andcured in an oven. After polymerization, the foam is post processed intothe appropriate device shape.

In an embodiment the SMP foams are crimped and attached to a deliverysystem. Several foam devices are inserted into the AAA sac via thedelivery system which navigates the foams through catheters placedwithin the aneurysm sac during the stent graft placement. Once theimplant is properly placed, the delivery system provides a stimulus toexpand the foam. This stimulus could be heated saline or solvent thatplasticizes the foam and causes it to expand. Heated saline or solventmay also be pumped through the delivery catheter. Alternatively, naturalbody temperature may serve as the stimulus for foam actuation. Theexpanded foam devices will fill the aneurysm volume between the stentgraft and aneurysm wall.

Another embodiment utilizes the foam, fabricated as described above, asan enhancement to existing stent grafts. In this case, SMP foam would bewrapped and crimped around the stent graft. The foam is fixed to thegraft material with an adhesive, or woven into the mesh network of thestent. The foam geometry may be a single annulus of bulk foam, orsegmented “scale” geometries that facilitate a small cross section afterdevice crimping. Segmented foam sections may also help minimize foamfolding and strain during stent delivery and deployment prior to the SMPfoam actuation.

Example 1b. A system comprising: a flexible conduit; first, second, andthird open-cell, polyurethane, thermoset, shape memory polymer (SMP)foams simultaneously included within the flexible conduit; a flexiblerod.

Even though this embodiment includes at least 3 SMP foams, otherembodiments may include a single SMP foam. For example, an embodimentincludes a single foam plug for biopsy occlusion. The physician removesa piece of tissue (e.g., biopsies a kidney, liver, or lung) and thenpushes a crimped SMP foam (e.g., shaped like a rod) through the biopsyneedle into the biopsy tissue track. Such a foam may include a markerband on its proximal end and the marker band will sit flush with theorgan surface once implanted.

Another embodiment may omit the flexible rod. For example, the conduitSMP foams may be included in a kit and the kit may not include theflexible rod. Instead, a physician may use some other rod from outsidethe kit to advance the SMP foams from the conduit.

Even though this embodiment includes at least 3 SMP foams, otherembodiments may include 1, 2, 4, 5 or more SMP foams within the conduit.

Such a “flexible conduit” may include an introducer.

Example 2b. The system of example 1b wherein: the flexible conduitincludes a proximal third, a middle third, and a distal third; thefirst, second, and third SMP foams are simultaneously included in thedistal third of the flexible conduit.

Example 3b. The system of example 2b wherein the first, second, andthird SMP foams are not fixedly coupled to each other.

Example 4b. The system of example 2b wherein the first, second, andthird SMP foams are configured to deploy from the flexible conduit suchthat they are not fixedly secured to one another immediately after theircollective deployment from the flexible conduit.

Example 5b. The system of example 2b wherein: in a first orientation thefirst, second, and third SMP foams are included in the distal third ofthe flexible conduit; in the first orientation the first, second, andthird SMP foams are coupled to each other via the flexible conduit butare not fixedly coupled to each other; in a second orientation thefirst, second, and third SMP foams are not coupled to each other afterthey are deployed from the flexible conduit.

Another version of Example 5b. The system of example 1b wherein: in afirst orientation the first, second, and third SMP foams aresubstantially evenly spaced throughout proximal, middle, and distalthirds of the flexible conduit; in the first orientation the first,second, and third SMP foams are coupled to each other via the flexibleconduit but are not fixedly coupled to each other; in a secondorientation the first, second, and third SMP foams are not coupled toeach other after they are deployed from the flexible conduit.

Example 6b. The system of example 2b wherein the first, second, andthird SMP foams are configured to deploy from the flexible conduit inserial fashion such that the first SMP foam deploys from the flexibleconduit before the second SMP foam and the second SMP foam deploys formthe flexible conduit before the third SMP foam.

Example 7b. The system according to any of examples 1b-6b wherein: thefirst, second, and third SMP foams respectively include first, second,and third metal portions; each of the first, second, and third SMP foamsincludes a long axis; the first SMP foam includes a proximal third, amiddle third, and a distal third; a first plane, which is orthogonal tothe long axis of the first SMP, which intersects the first metal portionand the proximal third of first SMP foam; the first metal portion doesnot extend to the middle and distal thirds of the first SMP foam.

Example 8b. The system of example 7b wherein: the first SMP foamincludes a second plane, which is orthogonal to the long axis of thefirst SMP, which intersects the middle third of first SMP foam but notany portion of the first metal portion; and the first SMP foam includesno backbone extending beyond the first metal portion.

Another version of Example 8b. The system of example 7b wherein: thefirst SMP foam includes a second plane, which is orthogonal to the longaxis of the first SMP, which intersects the middle third of first SMPfoam but not any portion of the first metal portion; and an outerperimeter of the first SMP foam intersects the second plane to form asingle closed perimeter; only SMP foam is included within the singleclosed perimeter.

Another version of Example 8b. The system of example 7b wherein: thefirst SMP foam includes a second plane, which is orthogonal to the longaxis of the first SMP, which intersects the middle third of the firstSMP foam but not any portion of the first metal portion; and the firstSMP foam may include a radiopaque backbone extending beyond the firstmetal portion.

The radiopaque backbone may be comprised of, for example, one or more ofthe following: platinum, tantalum, iridium, tungsten, polyurethane dopedwith metallic nanoparticles

Another version Example 8b. The system of example 7b wherein: the firstSMP foam includes a second plane, which is orthogonal to the long axisof the first SMP, which intersects the middle third of first SMP foambut not any portion of the first metal portion; and an outer perimeterof the first SMP foam intersects the second plane to form a singleclosed perimeter; SMP foam and a radiopaque backbone is included withinthe single closed perimeter.

Example 9b. The system of example 2b wherein the first, second, andthird SMP foams are fixedly coupled to each other.

Example 10b. The system of example 9b wherein a monolithic length ofmaterial extends through the first, second, and third SMP foams tocouple the first, second, and third SMP foams to one another.

Example 11b. The system of example 10b wherein the monolithic length ofmaterial includes at least one of a polymer and a metal.

Another version of Example 11b. The system of example 11b wherein themonolithic length of material includes a filament.

As used herein a filament includes a slender threadlike object or fiber.For example, a filament may include a thin metal wire or a thread madefrom a polymer.

Another version of Example 11b. The system of example 1b wherein each ofthe first, second, and third SMP foams are (a) crimped, and (b) between0 and 3 mm in diameter when crimped and between 8 and 30 mm in diameterwhen actuated into their primary state.

Another version of Example 11b. The system of example 1b wherein each ofthe first, second, and third SMP foams are (a) crimped, and (b) between0 and 3 mm in diameter when crimped and between 3 and 30 mm in diameterwhen actuated into their primary state.

In other embodiments the crimped diameter is between 0 and 2 mm, 0 and 4mm, 0 and 5 mm, or more. In other embodiments the actuated diameter isbetween 2 and 30 mm, 2 and 40, 2 and 50 mm, or more.

Another version of Example 11b. The system of example 1 wherein: thefirst SMP foam is covalently bonded to iodine; the first SMP foam isconfigured to expand from a compressed secondary state to an expandedprimary state in response to thermal stimulus, and the first SMP foam isa poly(urethane-urea-amide).

Example 11c. The system of example 11b wherein the SMP foam isradiopaque.

Example 11d. The system according to any of examples 11b-11c wherein theiodine is included in a triiodobenzene monomer.

Example 11e. The system of example 11d wherein the triiodobenzenemonomer includes at least one of (a) 5-amino-2,4,6-triiodoisophthalicacid (ATIPA), (b) diatrizoic acid, (c) iohexol, and (d) triiodophenol.

Example 12b. A method comprising: reacting a polyol with an isocyanateto form a reaction product; mixing the reaction product with a blowingagent to form an open-cell, polyurethane, thermoset, shape memorypolymer (SMP) foam; forming first, second, and third SMP foams from theSMP foam; coupling radiopaque materials to proximal portions of each ofthe first, second, and third SMP foams; including the first, second, andthird SMP foams simultaneously within a distal third of a flexibleconduit; after including the first, second, and third SMP foamssimultaneously within a distal third of a flexible conduit, sealing theflexible conduit and the first, second, and third SMP foams within ahermetically sealed storage container.

Example 13b. The method of example 12b wherein: the polyol includes atleast one of triethanolamine (TEA), diethanolamine, butane diol, butynediol, N,N,N′,N′ tetrakis (hydroxyl propylene) ethylenediamine (HPED),and combinations thereof; and the isocyanate includes at least one ofhexamethylene diisocyanate (HDI), trimethyl hexamethylene diisocyanate(TMHDI), isophorone diisocyanate (IPDI), and combinations thereof.

Another version of Example 13b includes: The method of example 12wherein: the polyol includes at least one of triethanolamine (TEA),diethanolamine, butane diol, N,N,N′,N′ tetrakis (hydroxyl propylene)ethylenediamine (HPED), and combinations thereof; and the isocyanateincludes at least one of hexamethylene diisocyanate (HDI), trimethylhexamethylene diisocyanate (TMHDI), isophorone diisocyanate (IPDI), andcombinations thereof.

Example 14b. The method of example 13b, wherein the isocyanate includesat least 85% HDI.

Example 15b. The method of example 14b, wherein the isocyanate includesat least 95% HDI.

Example 16b. The method according to any of examples 13b-15b wherein thepolyol includes at least 70% TEA.

Example 17b. The method according to example 16b wherein the polyolincludes at least 80% TEA.

Example 18b. The method according to any of examples 12b-17b wherein thefirst SMP foam includes metal nanoparticles.

Embodiments for Examples 1b through 11e include a flexible conduit.However, other embodiments are not so limited. For example, anotherversion of example 1 includes:

Example 19b. A system comprising: a conduit; first, second, and thirdopen-cell, polyurethane, thermoset, shape memory polymer (SMP) foamssimultaneously included within the flexible conduit.

The conduit may be stiff, like a needle. For example, the first, second,and third SMP foams (and fourth, fifth SMP foams or more) could bepreloaded into such a needle and then delivered to an aneurysm sac viatranslumbar puncture with the needle. A rod could be forced through theneedle to deploy the foams. Thus, embodiments allow for the examples 1to 11g to have such a stiff conduit substituted for the flexibleconduit.

An embodiment includes flexible conduit and a stiff needle. The flexibleconduit is pushed through the needle. The flexible conduit includes oneor more SMP foams which may be deployed from the needle using a pusherelement.

Embodiments may have SMP foams subjected to plasma surface treatments,changes in monomers, and the incorporation of water labile linkages intothe polymer backbone that biodegrade via hydrolysis. Tissue ingrowthcould be stimulated by the bulk or surface chemistry of the implant, orby initial thermal or chemical stimulus to the endothelium from the foamactuation mechanism.

Example 1c. A system comprising: a flexible conduit that simultaneouslyincludes: (a) a first open-cell, polyurethane, thermoset, shape memorypolymer (SMP) foam; (b) a second open-cell, polyurethane, thermoset, SMPfoam; and (c) a third open-cell, polyurethane, thermoset, SMP foam;wherein (a) the first SMP foam includes first and second ends thatoppose each other, (b) the second SMP foam includes first and secondends that oppose each other, and (c) the third SMP foam includes firstand second ends that oppose each other; wherein (a) the first SMP foamincludes a first backbone that extends from the first end of the firstSMP foam to the second end of the first SMP foam; (b) the second SMPfoam includes a second backbone that extends from the first end of thesecond SMP foam to the second end of the second SMP foam; (a) the thirdSMP foam includes a third backbone that extends from the first end ofthe third SMP foam to the second end of the third SMP foam; wherein (a)the first, second, and third SMP foams are not fixedly coupled to eachother; (b) the first, second, and third SMP foams are configured todeploy from the flexible conduit such that they are not fixedly securedto one another immediately after their collective deployment from theflexible conduit, and (c) the first, second, and third SMP foams areconfigured to deploy from the flexible conduit in serial fashion suchthat the first SMP foam deploys from the flexible conduit before thesecond SMP foam and the second SMP foam deploys form the flexibleconduit before the third SMP foam; wherein (a) the first backboneincludes at least one of platinum, tantalum, iridium, tungsten, orpolyurethane, (b) the second backbone includes at least one of platinum,tantalum, iridium, tungsten, or polyurethane, (c) the third backboneincludes at least one of platinum, tantalum, iridium, tungsten, orpolyurethane; wherein (a) the first SMP foam is between 0 and 3 mm indiameter, (b) the second SMP foam is between 0 and 3 mm in diameter, and(c) the third SMP foam is between 0 and 3 mm in diameter.

As used herein, a “flexible conduit” may have the flexibility of anintroducer made from a polymer, such as polyether ether ketone (PEEK).However, a “rigid conduit” may have the flexibility of a metal biopsyneedle of 15-19 gauge.

Example 2c. The system of example 1c wherein: (a) the first backboneincludes a monolithic length of material that extends from the first endof the first SMP foam to the second end of the first SMP foam, (b) thesecond backbone includes a monolithic length of material that extendsfrom the first end of the second SMP foam to the second end of thesecond SMP foam, and (c) the third backbone includes a monolithic lengthof material that extends from the first end of the third SMP foam to thesecond end of the third SMP foam.

Example 3c. The system of example 2c wherein the monolithic length ofmaterial of the first backbone includes at least one of a filament and acoil.

Example 4c. The system of example 3c wherein the first SMP foamincludes: (a) at least one of Hexamethylene Diisocyanate (HDI) orTrimethyl Hexamethylene Diisocyanate (TMHDI), and (b) at least one ofN,N,N′,N′-Tetrakis(2-Hydroxypropyl)ethylenediamine (HPED) orTriethanolamine (TEA).

Such a foam may be degradable.

Another version of Example 4c. The system of example 3c wherein thefirst SMP foam includes a reaction product of: (a) at least one ofHexamethylene Diisocyanate (HDI) or Trimethyl Hexamethylene Diisocyanate(TMHDI), and (b) at least one ofN,N,N′,N′-Tetrakis(2-Hydroxypropyl)ethylenediamine (HPED) orTriethanolamine (TEA).

Example 5c. The system of example 3c wherein the first SMP foamincludes: (a) at least one of Hexamethylene Diisocyanate (HDI) orTrimethyl Hexamethylene Diisocyanate (TMHDI), and (b) at least one ofGlycerol; 1,2,6-hexanetriol (HT); 3-methyl-1,5-pentanediol (MPD); or2-butyl-2-ethyl propanediol (BEP).

For example, the foam may be formed from HDI and HT monomers. Thosemonomers react before polymerization is complete. However, as usedherein, such a polymer foam would be said to include HDI and HT.

Such a foam may be non-degradable and mechanically tougher than the foamof Example 4c.

Another version of Example 5c. The system of example 3c wherein thefirst SMP foam includes: a reaction product of (a) at least one ofHexamethylene Diisocyanate (HDI) or Trimethyl Hexamethylene Diisocyanate(TMHDI), and (b) at least one of Glycerol; 1,2,6-hexanetriol (HT);3-methyl-1,5-pentanediol (MPD); or 2-butyl-2-ethyl propanediol (BEP).

Example 6c. The system of example 3c wherein the first SMP foamincludes: (a) at least one of Hexamethylene Diisocyanate (HDI) orTrimethyl Hexamethylene Diisocyanate (TMHDI), (b) at least one ofGlycerol; 1,2,6-hexanetriol (HT); 3-methyl-1,5-pentanediol (MPD); or2-butyl-2-ethyl propanediol (BEP), and (c) at least one of5-amino-2,4,6-triiodoisophthalic acid (ATIPA), Iohexol, orTriiodophenol.

Another version of Example 6c. The system of example 3c wherein thefirst SMP foam includes a reaction product of: (a) at least one ofHexamethylene Diisocyanate (HDI) or Trimethyl Hexamethylene Diisocyanate(TMHDI), (b) at least one of Glycerol; 1,2,6-hexanetriol (HT);3-methyl-1,5-pentanediol (MPD); or 2-butyl-2-ethyl propanediol (BEP),and (c) at least one of 5-amino-2,4,6-triiodoisophthalic acid (ATIPA),Iohexol, or Triiodophenol.

Such a foam may be x-ray visible, non-degradable and mechanicallytougher than the foam of Example 4c.

Example 6c′. A method comprising: reacting a polyol with an isocyanateto form a reaction product; mixing the reaction product with a blowingagent to form an open-cell, polyurethane, thermoset, shape memorypolymer (SMP) foam according to any of examples 4c, 5c, 6c; formingfirst, second, and third SMP foams from the SMP foam; including thefirst, second, and third SMP foams simultaneously within a conduit;after including the first, second, and third SMP foams simultaneouslywithin the conduit, sealing the conduit and the first, second, and thirdSMP foams within a hermetically sealed storage container.

Example 7c. The system of example 3c wherein (a) the first SMP foam hasa length between 7 mm and 25 mm, (b) the second SMP foam has a lengthbetween 7 mm and 25 mm, and (c) the third SMP foam has a length between7 mm and 25 mm.

Applicant determined this to be a critical range for some embodiments.Foams shorter than 7 mm exhibit undesirable occlusion and foams longerthan 25 mm are overly rigid and difficult to maneuver through tortuousvasculature.

Example 8c. The system of example 7c wherein: the flexible conduitincludes a length; the first, second, and third SMP foams arecollectively distributed across more than a third of the length of theflexible conduit.

Example 9c. The system of example 1c wherein: the first SMP foam iscovalently bonded to iodine; the first SMP foam is configured to expandfrom a compressed secondary state to an expanded primary state inresponse to thermal stimulus, and the first SMP foam is apoly(urethane-urea-amide).

Another version of Example 9c. The system of example 1c wherein: thefirst SMP foam is covalently bonded to iodine; and the first SMP foam isconfigured to expand from a compressed secondary state to an expandedprimary state in response to thermal stimulus.

Example 10c. The system of example 9c wherein the SMP foam isradiopaque.

Example 11c. The system of example 9c wherein the iodine is included ina triiodobenzene monomer.

Another version of Example 11c. The system of example 9c wherein theiodine is a reaction product of a triiodobenzene monomer.

Example 12c. The system of example 11c wherein the triiodobenzenemonomer includes at least one of (a) 5-amino-2,4,6-triiodoisophthalicacid (ATIPA), (b) diatrizoic acid, (c) iohexol, or (d) triiodophenol.

Example 13c. The system of example 1c wherein: in a first orientationthe first, second, and third SMP foams are coupled to each other via theflexible conduit but are not fixedly coupled to each other; in a secondorientation the first, second, and third SMP foams are not coupled toeach other after they are deployed from the flexible conduit.

Example 14c. A system comprising: a flexible conduit that includes anopen-cell, polyurethane, thermoset, shape memory polymer (SMP) foam;wherein the SMP foam is between 0 and 3 mm in diameter.

For instance, the 0 and 3 mm range is critical in that for certainembodiments the foam must have a structure that allows for suchcompressions such that the foam can be deployed via a catheter (e.g.,5F) and through tortuous vasculature. This separates foams describedherein from many conventional embolic materials.

Another version of Example 14c. A system comprising: a flexible conduitthat includes an open-cell, polyurethane, thermoset, shape memorypolymer (SMP) foam; wherein the SMP foam is between 0 and 3 mm indiameter; wherein the SMP foam includes first and second cells whichdirectly contact each other; wherein (a)(i) the first and second cellsshare and directly contact a ring of struts that provide structuralsupport for the first and second cells, (a)(ii) a membrane directlycontacts the ring of struts, and (a)(iii) the membrane is partiallyreticulated but not fully reticulated; wherein the partially reticulatedmembrane includes: (b)(i) a void that forms a path configured to allowfluid to flow between the first and second cells, (b)(ii) an interface,between the partially reticulated membrane and the void, which is roughand uneven; wherein the foam includes cells, including the first andsecond cells, which are anisotropic in shape and have unequal major andminor axes; wherein: (a) the ring of struts defines an outer perimeterof the membrane and the void defines an inner perimeter of the membrane;(b) an outer membrane area for the membrane is an area bounded by theouter perimeter defining an area of the membrane before reticulation;(c) a void area is an area bounded by the inner perimeter defining anarea of the void; and (d) the void area is between 25% and 75% of theouter membrane area.

Example 15c. The system of example 14c wherein the SMP foam includes:(a) at least one of Hexamethylene Diisocyanate (HDI) or TrimethylHexamethylene Diisocyanate (TMHDI), and (b) at least one of Glycerol;1,2,6-hexanetriol (HT); 3-methyl-1,5-pentanediol (MPD); or2-butyl-2-ethyl propanediol (BEP).

Another version of Example 15c. The system of example 14c wherein theSMP foam includes a reaction product of: (a) at least one ofHexamethylene Diisocyanate (HDI) or Trimethyl Hexamethylene Diisocyanate(TMHDI), and (b) at least one of Glycerol; 1,2,6-hexanetriol (HT);3-methyl-1,5-pentanediol (MPD); or 2-butyl-2-ethyl propanediol (BEP).

Example 16c. The system of example 14c wherein the SMP foam includes:(a) at least one of Hexamethylene Diisocyanate (HDI) or TrimethylHexamethylene Diisocyanate (TMHDI), (b) at least one of Glycerol;1,2,6-hexanetriol (HT); 3-methyl-1,5-pentanediol (MPD); or2-butyl-2-ethyl propanediol (BEP), and (c) at least one of5-amino-2,4,6-triiodoisophthalic acid (ATIPA), Iohexol, orTriiodophenol.

Another version of Example 16c. The system of example 14c wherein theSMP foam includes a reaction product of: (a) at least one ofHexamethylene Diisocyanate (HDI) or Trimethyl Hexamethylene Diisocyanate(TMHDI), (b) at least one of Glycerol; 1,2,6-hexanetriol (HT);3-methyl-1,5-pentanediol (MPD); or 2-butyl-2-ethyl propanediol (BEP),and (c) at least one of 5-amino-2,4,6-triiodoisophthalic acid (ATIPA),Iohexol, or Triiodophenol.

Example 17c. The system of example 14c wherein the SMP foam is:covalently bonded to iodine; configured to expand from a compressedsecondary state to an expanded primary state in response to thermalstimulus; and a poly(urethane-urea-amide).

Example 18c. The system of example 17c wherein the SMP foam isradiopaque.

Example 19c. The system of example 17c wherein the iodine is included ina triiodobenzene monomer.

Example 20c. The system of example 19c wherein the triiodobenzenemonomer includes at least one of (a) 5-amino-2,4,6-triiodoisophthalicacid (ATIPA), (b) diatrizoic acid, (c) iohexol, or (d) triiodophenol.

Example 21c. The system of example 14c wherein: the SMP foam includes aplane, which is orthogonal to a long axis of the SMP foam and whichintersects a middle third of the SMP foam; an outer perimeter of the SMPfoam intersects the second plane to form a single closed perimeter; onlySMP foam is included within the single closed perimeter.

Such a system includes no backbone.

Example 22c. A system comprising: a stiff conduit that includes anopen-cell, polyurethane, thermoset, shape memory polymer (SMP) foam;wherein the SMP foam is between 0 and 3 mm in diameter; wherein the SMPfoam includes first and second cells which directly contact each other;wherein (a)(i) the first and second cells share and directly contact aring of struts that provide structural support for the first and secondcells, (a)(ii) a membrane directly contacts the ring of struts, and(a)(iii) the membrane is partially reticulated but not fullyreticulated; wherein the partially reticulated membrane includes: (b)(i)a void that forms a path configured to allow fluid to flow between thefirst and second cells, (b)(ii) an interface, between the partiallyreticulated membrane and the void, which is rough and uneven; whereinthe foam includes cells, including the first and second cells, which areanisotropic in shape and have unequal major and minor axes; wherein: (a)the ring of struts defines an outer perimeter of the membrane and thevoid defines an inner perimeter of the membrane; (b) an outer membranearea for the membrane is an area bounded by the outer perimeter definingan area of the membrane before reticulation; (c) a void area is an areabounded by the inner perimeter defining an area of the void; and (d) thevoid area is between 25% and 75% of the outer membrane area.

The stiff conduit may be used as a biopsy needle.

Example 23c. A system comprising: a stiff conduit that simultaneouslyincludes: (a) a first open-cell, polyurethane, thermoset, shape memorypolymer (SMP) foam; (b) a second open-cell, polyurethane, thermoset, SMPfoam; and (c) a third open-cell, polyurethane, thermoset, SMP foam;wherein (a) the first SMP foam includes first and second ends thatoppose each other, (b) the second SMP foam includes first and secondends that oppose each other, and (c) the third SMP foam includes firstand second ends that oppose each other; wherein (a) the first SMP foamincludes a first backbone that extends from the first end of the firstSMP foam to the second end of the first SMP foam; (b) the second SMPfoam includes a second backbone that extends from the first end of thesecond SMP foam to the second end of the second SMP foam; (a) the thirdSMP foam includes a third backbone that extends from the first end ofthe third SMP foam to the second end of the third SMP foam; wherein (a)the first, second, and third SMP foams are not fixedly coupled to eachother; (b) the first, second, and third SMP foams are configured todeploy from the stiff conduit such that they are not fixedly secured toone another immediately after their collective deployment from the stiffconduit, and (c) the first, second, and third SMP foams are configuredto deploy from the stiff conduit in serial fashion such that the firstSMP foam deploys from the stiff conduit before the second SMP foam andthe second SMP foam deploys form the stiff conduit before the third SMPfoam; wherein (a) the first backbone includes at least one of platinum,tantalum, iridium, tungsten, or polyurethane, (b) the second backboneincludes at least one of platinum, tantalum, iridium, tungsten, orpolyurethane, (c) the third backbone includes at least one of platinum,tantalum, iridium, tungsten, or polyurethane; wherein (a) the first SMPfoam is between 0 and 3 mm in diameter, (b) the second SMP foam isbetween 0 and 3 mm in diameter, and (c) the third SMP foam is between 0and 3 mm in diameter.

The stiff conduit may be used as a biopsy needle.

Example 24c. A method comprising: implant a stent and a wire within ananeurysm; place a conduit over the wire; deliver a SMP foam via thecatheter, wherein the SMP via includes the first SMP foam of Example 1c;expand the SMP foam to conform the SMP foam to the aneurysm wall.

Example 25c. A method comprising: implant a stent and a wire within ananeurysm; place a conduit over the wire; deliver a SMP foam via thecatheter, wherein the SMP via includes the SMP foam of Example 14c;expand the SMP foam to conform the SMP foam to the aneurysm wall.

Example 26c. A method comprising: implant a stent and a wire within ananeurysm; place a conduit over the wire; deliver a SMP foam via thecatheter, wherein the SMP via includes the first SMP foam according toany of Examples 4c, 5c, 6c; expand the SMP foam to conform the SMP foamto the aneurysm wall.

Example 27c. A method comprising: implant a stent and a wire within ananeurysm; place a conduit over the wire; deliver a SMP foam via thecatheter, wherein the SMP via includes the SMP foam according to any ofExamples 15c, 16c, 17c, 18c, 19c, 20c; expand the SMP foam to conformthe SMP foam to the aneurysm wall.

Example 28c. A method comprising: reacting a polyol with an isocyanateto form a reaction product; mixing the reaction product with a blowingagent to form an open-cell, polyurethane, thermoset, shape memorypolymer (SMP) foam according to any of examples 15c, 16c, 17c, 18c, 19c,20c; including the SMP foam within a conduit; after including the SMPfoam within the conduit, sealing the conduit and the SMP foam within ahermetically sealed storage container.

Persons skilled in the relevant art can appreciate that manymodifications and variations are possible in light of the aboveteaching. Persons skilled in the art will recognize various equivalentcombinations and substitutions for various components shown in theFigures. It is therefore intended that the scope of the invention belimited not by this detailed description, but rather by the claimsappended hereto.

1. A system comprising: a conduit that simultaneously includes: (a) afirst open-cell, polyurethane, thermoset, shape memory polymer (SMP)foam; (b) a second open-cell, polyurethane, thermoset, SMP foam; and (c)a third open-cell, polyurethane, thermoset, SMP foam; wherein (a) thefirst SMP foam includes first and second ends that oppose each other,(b) the second SMP foam includes first and second ends that oppose eachother, and (c) the third SMP foam includes first and second ends thatoppose each other; wherein (a) the first SMP foam includes a firstbackbone that extends from the first end of the first SMP foam to thesecond end of the first SMP foam; (b) the second SMP foam includes asecond backbone that extends from the first end of the second SMP foamto the second end of the second SMP foam; (a) the third SMP foamincludes a third backbone that extends from the first end of the thirdSMP foam to the second end of the third SMP foam; wherein (a) the first,second, and third SMP foams are not fixedly coupled to each other; (b)the first, second, and third SMP foams are configured to deploy from theconduit such that they are not fixedly secured to one anotherimmediately after their collective deployment from the conduit, and (c)the first, second, and third SMP foams are configured to deploy from theconduit in serial fashion such that the first SMP foam deploys from theconduit before the second SMP foam and the second SMP foam deploys formthe conduit before the third SMP foam; wherein (a) the first backboneincludes at least one of platinum, tantalum, iridium, tungsten, orpolyurethane, (b) the second backbone includes at least one of platinum,tantalum, iridium, tungsten, or polyurethane, (c) the third backboneincludes at least one of platinum, tantalum, iridium, tungsten, orpolyurethane wherein (a) the first SMP foam is between 0 and 3 mm indiameter, (b) the second SMP foam is between 0 and 3 mm in diameter, and(c) the third SMP foam is between 0 and 3 mm in diameter.
 2. The systemof claim 1 wherein: (a) the first backbone includes a monolithic lengthof material that extends from the first end of the first SMP foam to thesecond end of the first SMP foam, (b) the second backbone includes amonolithic length of material that extends from the first end of thesecond SMP foam to the second end of the second SMP foam, and (c) thethird backbone includes a monolithic length of material that extendsfrom the first end of the third SMP foam to the second end of the thirdSMP foam.
 3. The system of claim 2 wherein the monolithic length ofmaterial of the first backbone includes at least one of a filament or acoil.
 4. The system of claim 3 wherein the first SMP foam includes: (a)at least one of Hexamethylene Diisocyanate (HDI) or TrimethylHexamethylene Diisocyanate (TMHDI), and (b) at least one ofN,N,N′,N′-Tetrakis(2-Hydroxypropyl)ethylenediamine (HPED) orTriethanolamine (TEA).
 5. The system of claim 3 wherein the first SMPfoam includes: (a) at least one of Hexamethylene Diisocyanate (HDI) orTrimethyl Hexamethylene Diisocyanate (TMHDI), and (b) at least one ofGlycerol; 1,2,6-hexanetriol (HT); 3-methyl-1,5-pentanediol (MPD); or2-butyl-2-ethyl propanediol (BEP).
 6. The system of claim 3 wherein thefirst SMP foam includes: (a) at least one of Hexamethylene Diisocyanate(HDI) or Trimethyl Hexamethylene Diisocyanate (TMHDI), (b) at least oneof Glycerol; 1,2,6-hexanetriol (HT); 3-methyl-1,5-pentanediol (MPD); or2-butyl-2-ethyl propanediol (BEP), and (c) at least one of5-amino-2,4,6-triiodoisophthalic acid (ATIPA), Iohexol, orTriiodophenol.
 7. The system of claim 3 wherein (a) the first SMP foamhas a length between 7 mm and 25 mm extending between the first andsecond ends of the first SMP foam, (b) the second SMP foam has a lengthbetween 7 mm and 25 mm extending between the first and second ends ofthe second SMP foam, and (c) the third SMP foam has a length between 7mm and 25 mm extending between the first and second ends of the thirdSMP foam.
 8. The system of claim 7 wherein: the conduit includes alength extending between first and second opposing ends of the conduit;the first, second, and third SMP foams are collectively distributedacross more than a third of the length of the conduit.
 9. The system ofclaim 1 wherein: the first SMP foam is covalently bonded to iodine; thefirst SMP foam is configured to expand from a compressed secondary stateto an expanded primary state in response to thermal stimulus; and thefirst SMP foam is a poly(urethane-urea-amide).
 10. The system of claim 9wherein the first SMP foam is radiopaque.
 11. The system of claim 9wherein the iodine is included in a triiodobenzene monomer.
 12. Thesystem of claim 11 wherein the triiodobenzene monomer includes at leastone of: (a) 5-amino-2,4,6-triiodoisophthalic acid (ATIPA), (b)diatrizoic acid, (c) iohexol, or (d) triiodophenol.
 13. The system ofclaim 1 wherein: in a first orientation the first, second, and third SMPfoams are coupled to each other via the conduit but are not fixedlycoupled to each other; in a second orientation the first, second, andthird SMP foams are not coupled to each other after they are deployedfrom the conduit.
 14. A system comprising: a conduit that includes anopen-cell, polyurethane, thermoset, shape memory polymer (SMP) foam;wherein the SMP foam is between 0 and 3 mm in diameter; wherein the SMPfoam includes first and second cells which directly contact each other;wherein (a)(i) the first and second cells share and directly contact aring of struts that provide structural support for the first and secondcells, (a)(ii) a membrane directly contacts the ring of struts, and(a)(iii) the membrane is partially reticulated but not fullyreticulated; wherein the partially reticulated membrane includes: (b)(i)a void that forms a path configured to allow fluid to flow between thefirst and second cells, (b)(ii) an interface, between the partiallyreticulated membrane and the void, which is rough and uneven; whereinthe foam includes cells, including the first and second cells, which areanisotropic in shape and have unequal major and minor axes; wherein: (a)the ring of struts defines an outer perimeter of the membrane and thevoid defines an inner perimeter of the membrane; (b) an outer membranearea for the membrane is an area bounded by the outer perimeter definingan area of the membrane before reticulation; (c) a void area is an areabounded by the inner perimeter defining an area of the void; and (d) thevoid area is between 25% and 75% of the outer membrane area.
 15. Thesystem of claim 14 wherein the SMP foam includes: (a) at least one ofHexamethylene Diisocyanate (HDI) or Trimethyl Hexamethylene Diisocyanate(TMHDI), and (b) at least one of Glycerol; 1,2,6-hexanetriol (HT);3-methyl-1,5-pentanediol (MPD); or 2-butyl-2-ethyl propanediol (BEP).16. The system of claim 14 wherein the SMP foam includes: (a) at leastone of Hexamethylene Diisocyanate (HDI) or Trimethyl HexamethyleneDiisocyanate (TMHDI), (b) at least one of Glycerol; 1,2,6-hexanetriol(HT); 3-methyl-1,5-pentanediol (MPD); or 2-butyl-2-ethyl propanediol(BEP), and (c) at least one of 5-amino-2,4,6-triiodoisophthalic acid(ATIPA), Iohexol, or Triiodophenol.
 17. The system of claim 14 whereinthe SMP foam is: covalently bonded to iodine; configured to expand froma compressed secondary state to an expanded primary state in response tothermal stimulus; and a poly(urethane-urea-amide).
 18. The system ofclaim 17 wherein the SMP foam is radiopaque.
 19. The system of claim 17wherein the iodine is included in a triiodobenzene monomer.
 20. Thesystem of claim 19 wherein the triiodobenzene monomer includes at leastone of (a) 5-amino-2,4,6-triiodoisophthalic acid (ATIPA), (b) diatrizoicacid, (c) iohexol, or (d) triiodophenol.
 21. The system of claim 14wherein: the SMP foam includes a plane, which is orthogonal to a longaxis of the SMP foam and which intersects a middle third of the SMPfoam; an outer perimeter of the SMP foam intersects the second plane toform a single closed perimeter; only SMP foam is included within thesingle closed perimeter.